Much of the recent work in the neurobiology of emotion has divided emotion into two categories of positive and negative emotion. Positive emotion is associated with approach behavior, while negative emotion is associated with avoidance. We have sought to characterize the neural substrates of approach and active avoidance behavior. Comparative studies have implicated a ventral forebrain dopaminergic path in approach behavior. We aimed primarily to verify activation of these areas in monetarily rewarded approach in humans and to determine if active avoidance behavior would elicit different patterns of activation Twelve healthy right-handed males (age 20-40) participated in 10-minute approach and active avoidance tasks in counterbalanced order. During the approach task, subjects pressed a button in response to a target which followed either a reward cue (On condition) or a neutral cue (motor controlled Off condition), ISI ~ 5.5 s. If subjects responded before the reward target disappeared, they won $1.00, whereas their response to the neutral target did not affect their total. During the active avoidance task, subjects were given $20.00 and responded to targets that followed either a punishment cue or a neutral cue. If they failed to respond before the disappearance of the punishment target, they lost $1.00, whereas their response to the neutral target again did not affect their total. 200 T2*-weighted gradient echoplanar MR volumes depicting BOLD-contrast were acquired using a 1.5 Tesla GE Signa System. The volume consisted of 10 slices spanning the corpus callosum (voxel size; 3.8 X 3.8 X 7.0 mm, TR: 3000 ms). After correcting for in-plane motion, individual voxel activations were correlated with an ideal waveform corresponding to the expected activation timecourse using AFNI. The ideal waveform consisted of the task On-Off waveform convoluted with the hemodynamic response function. Significant voxels (r < .30, p < .0001) were highlighted on the functional images. For the approach task, significant activation was observed in the mesial prefrontal cortex, striatum, dorsomedial thalamus , right insula, and motor cortex. For the active avoidance task, a similar but more robust pattern of activation was observed. Relative to approach, active avoidance elicited increased the volume of brain activated in all subjects. As predicted, monetarily rewarded approach elicited activation in ventral medial areas (including the striatum and thalamus), as well as more dorsal medial regions (i.e., mesial prefrontal cortex). Monetarily punished active avoidance appeared to elicit eve greater activation in these areas, as well as cingulate areas. These data provide the first neural corroboration of the psychological phenomenon of loss aversion, since subjects had a "greater" neural response to loss than to an equivalent expected gain. Similar studies are beginning with alcoholic subjects to determine if alcoholics possess different patterns of cerebral activation related to reward and punishment.